Fungicides and bactericides



Patented June 5, 1934 UNITED STATES FUNGICIDES AND nac'ramomas Earl B. Alvord, Cleveland Heights, Ohio, assignor to'The Grasselli Chemical Company, Cleveland,

Ohio, a corporation of Delaware No Drawing. Application July 18, 1931, Serial No. 551,792

10 Claims. (Cl. 167--33) The greatest enemies to human well being and their supply of foodstuffs are insects and microorganisms. Considerable efiort and ingenuity have been expended on finding ways and means to fight such parasites. In that part of the fight which is particularly directed to the preservation of vegetable life and vegetable matter it has in most instances been found that micro-organisms and insects have to be fought with different weapons, which is, of course, quite natural when one considers the different organization, mode of living' and size of micro-organisms and insects. While chemical means are some of the most common weapons employed in our war against msects and micro-organisms, it is only in exceptional cases that the same chemical will be effective against both insects and microorganisms without being toxic to higher forms of life. Considering the protection of living plants, we see that arsenicals, nicotine, and in more recent times fluosilicates or fluorides have been of invaluable help in the protection against various insects, whereas these same materials are practically powerless in the protection from the On the other hand, the commonest fungicide, sulfur, does in no manner hamper the development of insects thriving on vegetable material.

It is shown by Elmer K. Bolton in an application for Letters Patent Ser. No. 551,791, filed on even date herewith that certain organic, heterocyclic carbon-nitrogemsulfur compounds have a specific toxic effect against aphids, fiies and other insect pests.

I have found "that chemicals belonging similarly to a class of organic heterocyclic carbonsulfur-nitrogen compounds are agents which are particularly suited to combat various microorganisms, such as fungi, or bacteria, and my invention comprises fungicides which are sub-- stances containing in their molecules a five membered heterocyclic carbon-sulfur-nitrogen ring to which is attached a salt forming group and certain of their derivatives.

Considering the complexity of the problem of protecting organized materials from the attack of both insects and micro-organism, one can easily realize the great practical advantage that will result from the use of a single type of material which will be effective in the control of insects, as well as fungi and bacteria.

My invention comprises therefor the use as bactericides and fungicides, that is to say for controlling micro-organisms, of a group of organic substances consisting of substances which nucleus.

contain in their molecule a heterocyclic five membered ring consisting of carbon, sulfur and nitrogen atoms and which have a salt forming substituent attached to the ring, or nucleus, their salts and esters, as well as the alkyl, aryl and acyl derivatives of their salt forming groups.

The arrangement of the atoms in the five membered ring and the other atoms or radicals attached to four of the members of the ring do not seem to be of fundamental importance in respect to the toxicity of the compounds towards fungi or bacteria, though these factors have a pronounced effect upon the degree of toxicity and other physical or chemical properties which influence the availability of the compounds for controlling micro-organisms.

Among the several species of heterocyclic, five membered ring compounds containing carbon, nitrogen and sulfur and carrying a salt forming group, the thiazole derivatives are both as to their toxicity and technical availability particularly adapted for use against micro-organisms.

The thiazoles can be represented by the skeleton formula s and the termthiazole is used for the purposes of a this invention irrespective of the saturation of the nucleus, that is to say formulation with single or double bonds between the atoms of the As a matter of fact, many of the thiazoles exhibit properties which at present are ex- 9 plained by the assumption that the compounds exist as an equilibrium between tautomericforms which can be formulated as keto and enol type compounds such as The salt forming groups which when attached to one of the carbon atoms of the five membered nucleus, whereby the bactericidal and fungicidal properties are fully developed, can be of an acidic or basic nature; the acidic groups can be exemplified by -SH, --0H, SCH2-COOH, and other carboxylic, etc. groups. The basic groups may be NH2 and its substitution products, such as alkyl, aryl, acyl, etc.

Aliphatic as well as aromatic thiazoles are easily accessible by relatively simple synthetic 5 Pseudo-thio-hydantoin, or 2-imino-4-thiazolidone 2,4-diketo-tetrahydro-thiazole, or 2,4-thiazoledione Hr-S O-NH Rhodanin CHr-S CBH lON 4-methyl-2-amino-thiazole on-s /O-NH| /ON CH3 l-amino-benzo-thiazole '30 N ONHz s 1-hydroxybenzo -thiazole o-on 40 5/ Mercapto-benzo-thiazole N c-sn s 1-amino-alpha-naphtho-thiazole s I \C 'NHI 5 -ethoxy-1-ammo-benzo-th1azole Q C-NH:

CzHaO 3-methyl-1-amino-benzo-thiazole 7 CH3 N \GNH| 5-chloro-l-amino-benzo-thiazole 1-4-diamino -benzo-thiazole 5-hydroxy-l-amino-benzo-thiaz'ole Benzthiazyl-thioglycollic-acid These compounds all contain the five membered thiazole nucleus and a salt forming group attached to one of the carbon atoms of the nucleus.

The toxicity of these compounds towards microorganisms is not limited to these basic or respectively acid substances, and their respective salts partake in this property. The amino-thiazoles can, for instance, be combined with hydrochloric, sulfuric and many other inorganic or organic acids to form salts which exhibit in a broad manner the toxic properties of the thiazole bases. Similarly the acidic thiazoles, such as the mercapto, hydroxy, carboxylic derivatives form stable salts with alkalies, ammonia, heavy metals, such as Cu, Hg, Zn, etc., organic bases, etc., and there no again the toxic properties are carried over into the salts.

It appears furthermore that the salt forming groups of the thiazoles can be substituted without materially affecting the toxicity of the thiazole nucleus. Esters, or ethers and anhydrids of the acidic thiazole have substantially similar toxicity to that of the free acids and their salts. Similarly the toxicity of amino-thiazoles is maintained in their derivatives in which the aminogroup carries hydrocarbon or acyl (0R) substituents.

The carrying over of the fungicidal properties from the straight, salt forming thiazoles, into their salts, esters and other substitution products is of great practical importance as it permits of changing the physical properties of the active material without substantially modifying its useful bactericidal and fungicidal properties and gives a great latitude in the methods of applying these substances to the control of microorganisms. Salt formation, esterification and other substitution in the salt forming group change the solubility of the substances in water, mineral oil and other vehicles used to disperse or apply the toxic substances to organized mate? rial, such as living plants, wood, textiles, etc.

01' greater importance is the fact that by combining a weak base with a strong acid a salt may be formed which shows an acid reaction in water, or vice versa, and it is thereby possible to su ply the same active substance in an alkaline or acid form, as may be desired, in view of the lesser or greater tolerance of various insects for acid or alkaline materials.

I The neutral organic derivatives are in general more easily emulsified and thereby become available in a form which may be better suited for particular applications.

My novel bactericides and fungicides are in 150 general suited for controlling various micro-organisms, such as fungi and bacteria which thrive upon organized materials, such as-living plants, wood, textiles and other materials fabricated from vegetable or animal tissues.

My novel agentsfor the control of micro-organisms are applied in mannerssimilar to agents used heretofore. For spraying plants I use aqueous solutions or suspensions. For wood preservation I impregnate the wood with aqueous or oily solutions or emulsions. I can also apply my agents in dust form with or without inert diluents or in admixture with other agents. The dust form is, for instance,-suited to treating seeds or other reproducing organisms of plants.

Excellent control of Fomes annosus, a fungus living on wood has," for instance, been obtained by applying aqueous solutions of 'mercaptobenzo thiazole and its salts oramino-benzothiazole and its substitution products and salts in concentration of 0.1% down to 0.01% to cultures of this fungus.

Excellent control has also been obtained on various pathogenicfungi by the application of aqueous solutions of amino, hydroxy, or mercaptothiazoles and their salts. A few of the fungi thriving on living plants against which thiazoles have been tested successfully are listed below.

Sclerotinia cinerea, a parasite on stone fruit, causing rot. controlled by aqueous solutions of 0.1% and less 5-ethoxy-1eamino-benzo-ithiazole hydrochloride, sodium salt of .mercaptobenzo-thiazole or .5- chlor-l-arnino-benzo thiazole.

Perfectcontrol has also been obtained by these same agents on Phoma pomi, the cause of .Brocks spot on apples, which resists sulfur, and on .Glomerella cingulata.

Germination has been completely suppressed when 0.1% aqueous solutions of 5-ethoxy-1- amino-thiazole hydrochloride were applied to cultures of Verticillium aZbo-atrum, a fungus foundon maple, elm, tomatoes, etc.; Phomopsis, the cause of twig blight on elm trees, Graphium ulmi, the cause of the Dutch elm disease, Thzelaoia basicola, a tobacco fungus, .Fusarium mom'liforme, a parasite of wheat and corn which is resistant to most fungicides.

On Botrytis cinerea a fungus, which causes, for instance, lettuce drop,

applications 'of aqueous solutions from 0.1 down" to 0.01% of 5-.ethoxy-l-amino thiazole hydro chloride, sodium salt of mercaptobenzothiazole and the hydrochloride of 5-chlor-1-amino-benzothiazole have produced complete control.

It is in general advisable in using myrnovel= fungicides in aqueous solution or suspension to add to the composition a substance which improves the distribution of the composition over the material to be protected. Suchsubstances are generally of the type of protective colloids or act as defiocculating and/or wetting agents. Sulfonated oils, gumsrgelatinous materials, soaps, caseinates, etc. have in general the properties desired. They are commonly called Spreaders and their use with my novel fungicides enhances in a remarkable manner the 'toxicity towards various micro-organisms.

Asa rule I prefer to use my novel fungicides in solution or suspension containing less than 1% of my active ingredients. I add to such compositions from A; to of a spreader, as these proportions were found to mostefl'ectively bring out the toxicity of the thiazolecompounds, though plified above is in no This was, for instance, successfully I quite commonly found of the carbon atoms of lesser or larger amounts can be used to advantagein many instances and depending on special circumstances.

The fungicidal experiments, the results of which are listed above, have all been made with compositions containing from A to spreader, such as a ifishoil soap or a mineral oil.

The fungicidal and sulfonated bactericidal action exemway limited to the specific compounds mentioned above, nor to the particular micro-organisms and it will be understood that my invention is not limited to these particular applicatons, but it is directed to the use generally of substances containing the five membered heterocyclic, carbon, sulfur, nitrogen ring which have a salt forming group attached to this nucleus and their salts, esters and other substitution products which I have found to be toxic towards various pathogenic micro-organisms thriving on organized materials.

While the toxicity towards micro-organisms seems to be general to substances containing the heterocyclic carbon, sulfur, nitrogen five membered ring, it appears from my present knowledge thatv such compounds are preferred in which '2 carbon atoms of the nucleus are parts of an aromatic ring and in which the 3rd carbon atom carries a sulfhydryl or amino substituent.

I claim:

1.. An'agentfor the control of pathogenic miere-organisms thriving .on organized materials comprising an, organic substance containing in its molecule a five membered ring composed of 3 carbons, one nitrogen and one sulfur atom, one of said carbon atoms carrying a salt forming "group.

2. An agent for the control of pathogenic micro-organisms thriving on organized materials comprising an organic substance containing in its molecule-the heterocyclic nucleus in which X is a salt-forming group.

its molecule the heterocyclic nucleus n l sc-x l in which X is a sa1t' forming'group and in which the other'two carbon atoms are parts of an'arovrnatic ring. Q

4. A wood preservative comprising a mercaptobenzothiazole salt.

5. A fungicide comprising an aqueous composition containing a spreader and a thiazole containing a salt forming group attached to one the .thiazole nucleus.

6. A fungicide comprising-an aqueous composition containing a spreader of the class of spreaders consisting of soaps and sulfonated oils and a thiazole containing a salt forming group attached to one of the carbon atoms of the thiazole nucleus.

'7. A fungicide and bactericide comprising a. 9. A fungicide and bactericide comprising a thiazole of the formula thiazoie of the formula N J -N 5 l -S-R 80 i in which R is hydrogen or an atom or atom in which X is one Of the elements N, O and S grouping which can replace hydrogen when it and. R is hydrogen or an atom or atom grouping exercises t acidic functions 5 w ic a ep a hydrogen when it exercises 10. A fungicide and bactericide comprising a its acidic functionsthiazole of the formula 8. A fungicide and bactericide comprising a thiazole of the formula N N R OR N in which R is hydrogen or an atom or atom grouping which can replace hydrogen when it 20 in which R is hydrogen, a hydrocarbon or an acyi exercises its acidic functions.

radical. EARL B. ALVORD. 

